Expression profile of tyrosine phosphatases in HER2 breast cancer cells and tumors

Maria Antonietta Lucci, Rosaria Orlandi, Tiziana Triulzi, Elda Tagliabue, Andrea Balsari, Emma Villa-Moruzzi

Research output: Contribution to journalArticle

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Abstract

Background: HER2-overexpression promotes malignancy by modulating signalling molecules, which include PTPs/DSPs (protein tyrosine and dual-specificity phosphatases). Our aim was to identify PTPs/DSPs displaying HER2-associated expression alterations. Methods: HER2 activity was modulated in MDA-MB-453 cells and PTPs/DSPs expression was analysed with a DNA oligoarray, by RT-PCR and immunoblotting. Two public breast tumor datasets were analysed to identify PTPs/DSPs differentially expressed in HER2-positive tumors. Results: In cells (1) HER2-inhibition up-regulated 4 PTPs (PTPRA, PTPRK, PTPN11, PTPN18) and 11 DSPs (7 MKPs [MAP Kinase Phosphatases], 2 PTP4, 2 MTMRs [Myotubularin related phosphatases]) and down-regulated 7 DSPs (2 MKPs, 2 MTMRs, CDKN3, PTEN, CDC25C); (2) HER2-activation with EGF affected 10 DSPs (5 MKPs, 2 MTMRs, PTP4A1, CDKN3, CDC25B) and PTPN13; 8 DSPs were found in both groups. Furthermore, 7 PTPs/DSPs displayed also altered protein level. Analysis of 2 breast cancer datasets identified 6 differentially expressed DSPs: DUSP6, strongly up-regulated in both datasets; DUSP10 and CDC25B, up-regulated; PTP4A2, CDC14A and MTMR11 down-regulated in one dataset. Conclusions: Several DSPs, mainly MKPs and, unexpectedly, MTMRs, were altered following HER2-modulation in cells and 3 DSPs (DUSP6, CDC25B and MTMR11) were altered in both cells and tumors. Among these, DUSP6, strongly up-regulated in HER2-positive tumors, would deserve further investigation as tumor marker or potential therapy target.

Original languageEnglish
Pages (from-to)361-372
Number of pages12
JournalCellular Oncology
Volume32
Issue number5-6
DOIs
Publication statusPublished - 2010

Fingerprint

Phosphoric Monoester Hydrolases
Tyrosine
Breast Neoplasms
Mitogen-Activated Protein Kinase 1
Neoplasms
Dual-Specificity Phosphatases
Tumor Biomarkers
Immunoblotting
Epidermal Growth Factor
Proteins
Phosphotransferases
Polymerase Chain Reaction
Datasets
DNA
Therapeutics

Keywords

  • array analysis
  • breast cancer
  • HER2
  • phosphorylation
  • Tyrosine phosphatases

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine

Cite this

Expression profile of tyrosine phosphatases in HER2 breast cancer cells and tumors. / Lucci, Maria Antonietta; Orlandi, Rosaria; Triulzi, Tiziana; Tagliabue, Elda; Balsari, Andrea; Villa-Moruzzi, Emma.

In: Cellular Oncology, Vol. 32, No. 5-6, 2010, p. 361-372.

Research output: Contribution to journalArticle

Lucci, Maria Antonietta ; Orlandi, Rosaria ; Triulzi, Tiziana ; Tagliabue, Elda ; Balsari, Andrea ; Villa-Moruzzi, Emma. / Expression profile of tyrosine phosphatases in HER2 breast cancer cells and tumors. In: Cellular Oncology. 2010 ; Vol. 32, No. 5-6. pp. 361-372.
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AU - Lucci, Maria Antonietta

AU - Orlandi, Rosaria

AU - Triulzi, Tiziana

AU - Tagliabue, Elda

AU - Balsari, Andrea

AU - Villa-Moruzzi, Emma

PY - 2010

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AB - Background: HER2-overexpression promotes malignancy by modulating signalling molecules, which include PTPs/DSPs (protein tyrosine and dual-specificity phosphatases). Our aim was to identify PTPs/DSPs displaying HER2-associated expression alterations. Methods: HER2 activity was modulated in MDA-MB-453 cells and PTPs/DSPs expression was analysed with a DNA oligoarray, by RT-PCR and immunoblotting. Two public breast tumor datasets were analysed to identify PTPs/DSPs differentially expressed in HER2-positive tumors. Results: In cells (1) HER2-inhibition up-regulated 4 PTPs (PTPRA, PTPRK, PTPN11, PTPN18) and 11 DSPs (7 MKPs [MAP Kinase Phosphatases], 2 PTP4, 2 MTMRs [Myotubularin related phosphatases]) and down-regulated 7 DSPs (2 MKPs, 2 MTMRs, CDKN3, PTEN, CDC25C); (2) HER2-activation with EGF affected 10 DSPs (5 MKPs, 2 MTMRs, PTP4A1, CDKN3, CDC25B) and PTPN13; 8 DSPs were found in both groups. Furthermore, 7 PTPs/DSPs displayed also altered protein level. Analysis of 2 breast cancer datasets identified 6 differentially expressed DSPs: DUSP6, strongly up-regulated in both datasets; DUSP10 and CDC25B, up-regulated; PTP4A2, CDC14A and MTMR11 down-regulated in one dataset. Conclusions: Several DSPs, mainly MKPs and, unexpectedly, MTMRs, were altered following HER2-modulation in cells and 3 DSPs (DUSP6, CDC25B and MTMR11) were altered in both cells and tumors. Among these, DUSP6, strongly up-regulated in HER2-positive tumors, would deserve further investigation as tumor marker or potential therapy target.

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KW - HER2

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